Investigating interventions to increase uptake of HIV testing and linkage into care or prevention for male partners of pregnant women in antenatal clinics in Blantyre, Malawi: study protocol for a cluster randomised trial.

BACKGROUND: Despite large-scale efforts to diagnose people living with HIV, 54% remain undiagnosed in sub-Saharan Africa. The gap in knowledge of HIV status and uptake of follow-on services remains wide with much lower rates of HIV testing among men compared to women. Here, we design a study to investigate the effect on uptake of HIV testing and linkage into care or prevention of partner-delivered HIV self-testing alone or with an additional intervention among male partners of pregnant women. METHODS: A phase II, adaptive, multi-arm, multi-stage cluster randomised trial, randomising antenatal clinic (ANC) days to six different trial arms. Pregnant women accessing ANC in urban Malawi for the first time will be recruited into either the standard of care (SOC) arm (invitation letter to the male partner offering HIV testing) or one of five intervention arms offering oral HIV self-test kits. Three of the five intervention arms will additionally offer the male partner a financial incentive (fixed or lottery amount) conditional on linkage after self-testing with one arm testing phone call reminders. Assuming that 25% of male partners link to care or prevention in the SOC arm, six clinic days, with a harmonic mean of 21 eligible participants, per arm will provide 80% power to detect a 0.15 absolute difference in the primary outcome. Cluster proportions will be analysed by a cluster summaries approach with adjustment for clustering and multiplicity. DISCUSSION: This trial applies adaptive methods which are novel and efficient designs. The methodology and lessons learned here will be important as proof of concept of how to design and conduct similar studies in the future. Although small, this trial will potentially present good evidence on the type of effective interventions for improving linkage into ART or prevention. The trial results will also have important policy implications on how to implement HIVST targeting male partners of pregnant women who are accessing ANC for the first time while paying particular attention to safety concerns. Contamination may occur if women in the intervention arms share their self-test kits with women in the SOC arm. TRIAL REGISTRATION: ISRCTN, ID: 18421340 . Registered on 31 March 2016

HIV self-testing services for female sex workers, Malawi and Zimbabwe

OBJECTIVE: To present findings from implementation and scale-up of human immunodeficiency virus (HIV) self-testing programmes for female sex workers in Malawi and Zimbabwe, 2013-2018. METHODS: In Zimbabwe, we carried out formative research to assess the acceptability and accuracy of HIV self-testing. During implementation we evaluated sex workers' preferences for, and feasibility of, distribution of test kits before the programme was scaled-up. In Malawi, we conducted a rapid ethnographic assessment to explore the context and needs of female sex workers and resources available, leading to a workshop to define the distribution approach for test kits. Once distribution was implemented, we conducted a process evaluation and established a system for monitoring social harm. FINDINGS: In Zimbabwe, female sex workers were able to accurately self-test. The preference study helped to refine systems for national scale-up through existing services for female sex workers. The qualitative data helped to identify additional distribution strategies and mediate potential social harm to women. In Malawi, peer distribution of test kits was the preferred strategy. We identified some incidents of social harm among peer distributors and female sex workers, as well as supply-side barriers to implementation which hindered uptake of testing. CONCLUSION: Involving female sex workers in planning and ongoing implementation of HIV self-testing is essential, along with strategies to mitigate potential harm. Optimal strategies for distribution and post-test support are context-specific and need to consider existing support for female sex workers and levels of trust and cohesion within their communities

'I will choose when to test, where I want to test': investigating young people's preferences for HIV self-testing in Malawi and Zimbabwe.

OBJECTIVES: The current study identifies young people's preferences for HIV self-testing (HIVST) delivery, determines the relative strength of preferences and explores underlying behaviors and perceptions to inform youth-friendly services in southern Africa. DESIGN: A mixed methods design was adopted in Malawi and Zimbabwe and includes focus group discussions, in-depth interviews and discrete choice experiments. METHODS: The current study was conducted during the formative phase of cluster-randomized trials of oral-fluid HIVST distribution. Young people aged 16-25 years were purposively selected for in-depth interviews (n = 15) in Malawi and 12 focus group discussions (n = 107) across countries. Representative samples of young people in both countries (n = 341) were administered discrete choice experiments on HIVST delivery, with data analyzed to estimate relative preferences. The qualitative results provided additional depth and were triangulated with the quantitative findings. RESULTS: There was strong concordance across methods and countries based on the three triangulation parameters: product, provider and service characteristics. HIVST was highly accepted by young people, if provided at no or very low cost. Young people expressed mixed views on oral-fluid tests, weighing perceived benefits with accuracy concerns. There was an expressed lack of trust in health providers and preference for lay community distributors. HIVST addressed youth-specific barriers to standard HIV testing, with home-based distribution considered convenient. Issues of autonomy, control, respect and confidentiality emerged as key qualitative themes. CONCLUSION: HIVST services can be optimized to reach young people if products are provided through home-based distribution and at low prices, with respect for them as autonomous individuals

COVID-19 self-testing using antigen rapid diagnostic tests: Feasibility evaluation among health-care workers and general population in Malawi

Background COVID-19 testing is critical for identifying cases to prevent transmission. COVID-19 self-testing has the potential to increase diagnostic testing capacity and to expand access to hard-to-reach areas in low-and-middle-income countries. We investigated the feasibility and acceptability of COVID-19 self-sampling and self-testing using SARS-CoV-2 Antigen-Rapid Diagnostic Tests (Ag-RDTs). Methods From July 2021 to February 2022, we conducted a mixed-methods cross-sectional study examining self-sampling and self-testing using Standard Q and Panbio COVID-19 Ag Rapid Test Device in Urban and rural Blantyre, Malawi. Health care workers and adults (18y+) in the general population were non-randomly sampled. Results Overall, 1,330 participants were enrolled of whom 674 (56.0%) were female and 656 (54.0%) were male with 664 for self-sampling and 666 for self-testing. Mean age was 30.7y (standard deviation [SD] 9.6). Self-sampling usability threshold for Standard Q was 273/333 (82.0%: 95% CI 77.4% to 86.0%) and 261/331 (78.8%: 95% CI 74.1% to 83.1%) for Panbio. Self-testing threshold was 276/335 (82.4%: 95% CI 77.9% to 86.3%) and 300/332 (90.4%: 95% CI 86.7% to 93.3%) for Standard Q and Panbio, respectively. Agreement between self-sample results and professional test results was 325/325 (100%) and 322/322 (100%) for Standard Q and Panbio, respectively. For self-testing, agreement was 332/333 (99.7%: 95% CI 98.3 to 100%) for Standard Q and 330/330 (100%: 95% CI 99.8 to 100%) for Panbio. Odds of achieving self-sampling threshold increased if the participant was recruited from an urban site (odds ratio [OR] 2.15 95% CI 1.44 to 3.23, P < .01. Compared to participants with primary school education those with secondary and tertiary achieved higher self-testing threshold OR 1.88 (95% CI 1.17 to 3.01), P = .01 and 4.05 (95% CI 1.20 to13.63), P = .02, respectively. Conclusions One of the first studies to demonstrate high feasibility and acceptability of self-testing using SARS-CoV-2 Ag-RDTs among general and health-care worker populations in low- and middle-income countries potentially supporting large scale-up. Further research is warranted to provide optimal delivery strategies of self-testing

Outcome Assessment of a Dedicated HIV Positive Health Care Worker Clinic at a Central Hospital in Malawi: A Retrospective Observational Study

BACKGROUND: Malawi has one of the world's lowest densities of Health Care Workers (HCW) per capita. This study evaluates outcomes of a dedicated HCW HIV clinic in Malawi, created at Zomba Central Hospital in January 2007. METHODS AND FINDINGS: Retrospective cohort data was analyzed comparing HCW clinic patient baseline characteristics and treatment outcomes at 18 months after inception, against those attending the general HIV clinic. In-depth interviews and focus group discussions were conducted to explore perceptions of patients and caregivers regarding program value, level of awareness and barriers for uptake amongst HCW. 306 patients were enrolled on antiretroviral therapy (ART) in the HCW HIV clinic, 6784 in the general clinic. Significantly (p<0.01) more HCW clients were initiated on ART on the basis of CD4 as opposed to WHO Stage 3/4 (36% vs.23%). Significantly fewer HCW clients defaulted (6% vs.17%), and died (4% vs.12%). The dedicated HCW HIV clinic was perceived as important and convenient in terms of reduced waiting times, and prompt and high quality care. Improved confidentiality was an appreciated quality of the HCW clinic however barriers included fear of being recognized. CONCLUSIONS/SIGNIFICANCE: Outcomes at the HCW clinic appear better compared to the general HIV clinic. The strategy of dedicated clinics to care for health providers is a means of HIV impact mitigation within human resource constrained health systems in high prevalence settings

Correlates of prior HIV testing and schistosomiasis treatment: Baseline survey findings from the “creating demand for fishermen’s schistosomiasis HIV services” (FISH) cluster-randomized trial in Mangochi, Malawi

Background: Fishing exposes fishermen to schistosomiasis-infested fresh water and concurrently through precarious livelihoods to risky sexual behaviour, rendering these two infections occupational hazards for fishermen. This study aimed to characterize the knowledge of the two conditions to obtain necessary data for a subsequent cluster randomized trial designed to investigate demand creation strategies for joint HIV-schistosomiasis service provision in fishing villages on the shores of southern Lake Malawi. Methods: Enumeration of all resident fishermen in 45 clusters (fishing communities) was carried out between November 2019 and February 2020. In a baseline survey, fishermen reported their knowledge, attitudes and practices in the uptake of HIV and schistosomiasis services. Knowledge of HIV status and previous receipt of praziquantel were modelled using random effects binomial regression, accounting for clustering. Prevalence of willingness to attend a beach clinic was computed. Results: A total of 6,297 fishermen were surveyed from the 45 clusters with harmonic mean number of fishermen per cluster of 112 (95% CI: 97; 134). The mean age was 31.7y (SD: 11.9) and nearly 40% (2,474/6,297) could not read or write. Overall, 1,334/6,293 (21.2%) had never tested for HIV, with 64.4% (3,191/4,956) having tested in the last 12 months, and 5.9% (373/6290) taking antiretroviral therapy (ART). In adjusted analyses, being able to read and write (adjusted risk ratio [aRR: 1.91, 95% CI: 1.59–2.29, p<0.001); previous use of praziquantel (aRR: 2.00,95% CI: 1.73–2.30, p<0.001); knowing a relative or friend who died of HIV (aRR: 1.54,95% CI: 1.33–1.79, p<0.001); and being on ART (aRR: 12.93, 95% CI: 6.25–32.93, p<0.001) were associated with increased likelihood of ever testing for HIV. Only 40% (1,733/4,465) had received praziquantel in the last 12 months. Every additional year of age was associated with 1% decreased likelihood of having taken praziquantel in the last 12 months (aRR: 0.99, 95% CI: 0.98–0.99, p<0.001). However, recent HIV testing increased the likelihood of taking praziquantel by over 2-fold (aRR 2.24, 95% CI: 1.93–2.62, p<0.001). Willingness to attend a mobile beach clinic offering integrated HIV and schistosomiasis services was extremely high at 99.0% (6,224/6,284). Conclusion: In a setting with an underlying high prevalence of both HIV and schistosomiasis, we found low knowledge of HIV status and low utilization of free schistosomiasis treatment. Among fishermen who accessed HIV services, there was a very high likelihood of taking praziquantel suggesting that integrated service delivery may lead to good coverage. Trial registration: This trial is registered in the ISRCTN registry: ISRCTN14354324; date of registration: 05 October 2020

Decentralized Heart Failure Management in Neno, Malawi

Background: Cardiovascular disease (CVD) is a major cause of death in Malawi. In rural districts, heart failure (HF) care is limited and provided by non-physicians. The causes and patient outcomes of HF in rural Africa are largely unknown. In our study, non-physician providers performed focused cardiac ultrasound (FOCUS) for HF diagnosis and longitudinal clinical follow-up in Neno, Malawi. Objectives: We described the clinical characteristics, HF categories, and outcomes of patients presenting with HF in chronic care clinics in Neno, Malawi. Methods: Between November 2018 and March 2021, non-physician providers performed FOCUS for diagnosis and longitudinal follow-up in an outpatient chronic disease clinic in rural Malawi. A retrospective chart review was performed for HF diagnostic categories, change in clinical status between enrollment and follow-up, and clinical outcomes. For study purposes, cardiologists reviewed all available ultrasound images. Results: There were 178 patients with HF, a median age of 67 years (IQR 44 – 75), and 103 (58%) women. During the study period, patients were enrolled for a mean of 11.5 months (IQR 5.1–16.5), after which 139 (78%) were alive and in care. The most common diagnostic categories by cardiac ultrasound were hypertensive heart disease (36%), cardiomyopathy (26%), and rheumatic, valvular or congenital heart disease (12.3%). At follow-up, the proportion of New York Heart Association (NYHA) class I patients increased from 24% to 50% (p < 0.001; 95% CI: 31.5 – 16.4), and symptoms of orthopnea, edema, fatigue, hypervolemia, and bibasilar crackles all decreased (p < 0.05). Conclusion: Hypertensive heart disease and cardiomyopathy are the predominant causes of HF in this elderly cohort in rural Malawi. Trained non-physician providers can successfully manage HF to improve symptoms and clinical outcomes in limited resource areas. Similar care models could improve healthcare access in other rural African settings

Ability to understand and correctly follow HIV self-test kit instructions for use: applying the cognitive interview technique in Malawi and Zambia.

INTRODUCTION: The ability to achieve an accurate test result and interpret it correctly is critical to the impact and effectiveness of HIV self-testing (HIVST). Simple and easy-to-use devices, instructions for use (IFU) and other support tools have been shown to be key to good performance in sub-Saharan Africa and may be highly contextual. The objective of this study was to explore the utility of cognitive interviewing in optimizing the local understanding of manufacturers' IFUs to achieve an accurate HIVST result. METHODS: Functionally literate and antiretroviral therapy-naive participants were purposefully selected between May 2016 and June 2017 to represent intended users of HIV self-tests from urban and rural areas in Malawi and Zambia. Participants were asked to follow IFUs for HIVST. We then conducted cognitive interviews and observed participants while they attempted to complete the HIVST steps using a structured guide, which mirrored the steps in the IFU. Qualitative data were analysed using a thematic approach. RESULTS: Of a total of 61 participants, many successfully performed most steps in the IFU. Some had difficulties in understanding these and made errors, which could have led to incorrect test results, such as incorrect use of buffer and reading the results prematurely. Participants with lower levels of literacy and inexperience with standard pictorial images were more likely to struggle with IFUs. Difficulties tended to be more pronounced among those in rural settings. Ambiguous terms and translations in the IFU, unfamiliar images and symbols, and unclear order of the steps to be followed were most commonly linked to errors and lower comprehension among participants. Feedback was provided to the manufacturer on the findings, which resulted in further optimization of IFUs. CONCLUSIONS: Cognitive interviewing identifies local difficulties in conducting HIVST from manufacturer-translated IFUs. It is a useful and practical methodology to optimize IFUs and make them more understandable

Pragmatic economic evaluation of community-led delivery of HIV self-testing in Malawi.

INTRODUCTION: Community-based strategies can extend coverage of HIV testing and diagnose HIV at earlier stages of infection but can be costly to implement. We evaluated the costs and effects of community-led delivery of HIV self-testing (HIVST) in Mangochi District, Malawi. METHODS: This economic evaluation was based within a pragmatic cluster-randomised trial of 30 group village heads and their catchment areas comparing the community-led HIVST intervention in addition to the standard of care (SOC) versus the SOC alone. The intervention involved mobilising community health groups to lead 7-day HIVST campaigns including distribution of HIVST kits. The SOC included facility-based HIV testing services. Primary costings estimated economic costs of the intervention and SOC from the provider perspective, with costs annualised and measured in 2018 US$. A postintervention survey captured individual-level data on HIV testing events, which were combined with unit costs from primary costings, and outcomes. The incremental cost per person tested HIV-positive and associated uncertainty were estimated. RESULTS: Overall, the community-led HIVST intervention costed$138 624 or $5.70 per HIVST kit distributed, with test kits and personnel the main contributing costs. The SOC costed$263 400 or $4.57 per person tested. Individual-level provider costs were higher in the community-led HIVST arm than the SOC arm (adjusted mean difference$3.77, 95% CI $2.44 to$5.10; p<0.001), while the intervention effect on HIV positivity varied based on adjustment for previous diagnosis. The incremental cost per person tested HIV positive was $324 but increased to$1312 and $985 when adjusting for previously diagnosed self-testers or self-testers on treatment, respectively. Community-led HIVST demonstrated low probability of being cost-effective against plausible willingness-to-pay values, with HIV positivity a key determinant. CONCLUSION: Community-led HIVST can provide HIV testing at a low additional unit cost. However, adding community-led HIVST to the SOC was not likely to be cost-effective, especially in contexts with low prevalence of undiagnosed HIV. TRIAL REGISTRATION NUMBER: NCT03541382

Effect of community-led delivery of HIV self-testing on HIV testing and antiretroviral therapy initiation in Malawi: A cluster-randomised trial

BACKGROUND: Undiagnosed HIV infection remains substantial in key population subgroups including adolescents, older adults, and men, driving ongoing transmission in sub-Saharan Africa. We evaluated the impact, safety, and costs of community-led delivery of HIV self-testing (HIVST), aiming to increase HIV testing in underserved subgroups and stimulate demand for antiretroviral therapy (ART). METHODS AND FINDINGS: This cluster-randomised trial, conducted between October 2018 and July 2019, used restricted randomisation (1:1) to allocate 30 group village head clusters in Mangochi district, Malawi to the community-led HIVST intervention in addition to the standard of care (SOC) or the SOC alone. The intervention involved mobilising community health groups to lead the design and implementation of 7-day HIVST campaigns, with cluster residents (≥15 years) eligible for HIVST. The primary outcome compared lifetime HIV testing among adolescents (15 to 19 years) between arms. Secondary outcomes compared: recent HIV testing (in the last 3 months) among older adults (≥40 years) and men; cumulative 6-month incidence of ART initiation per 100,000 population; knowledge of the preventive benefits of HIV treatment; and HIV testing stigma. Outcomes were measured through a post-intervention survey and at neighboring health facilities. Analysis used intention-to-treat for cluster-level outcomes. Community health groups delivered 24,316 oral fluid-based HIVST kits. The survey included 90.2% (3,960/4,388) of listed participants in the 15 community-led HIVST clusters and 89.2% (3,920/4,394) of listed participants in the 15 SOC clusters. Overall, the proportion of men was 39.0% (3,072/7,880). Most participants obtained primary-level education or below, were married, and reported a sexual partner. Lifetime HIV testing among adolescents was higher in the community-led HIVST arm (84.6%, 770/910) than the SOC arm (67.1%, 582/867; adjusted risk difference [RD] 15.2%, 95% CI 7.5% to 22.9%; p < 0.001), especially among 15 to 17 year olds and boys. Recent testing among older adults was also higher in the community-led HIVST arm (74.5%, 869/1,166) than the SOC arm (31.5%, 350/1,111; adjusted RD 42.1%, 95% CI 34.9% to 49.4%; p < 0.001). Similarly, the proportions of recently tested men were 74.6% (1,177/1,577) and 33.9% (507/1,495) in the community-led HIVST and SOC arms, respectively (adjusted RD 40.2%, 95% CI 32.9% to 47.4%; p < 0.001). Knowledge of HIV treatment benefits and HIV testing stigma showed no differences between arms. Cumulative incidence of ART initiation was respectively 305.3 and 226.1 per 100,000 population in the community-led HIVST and SOC arms (RD 72.3, 95% CI -36.2 to 180.8; p = 0.18). In post hoc analysis, ART initiations in the 3-month post-intervention period were higher in the community-led HIVST arm than the SOC arm (RD 97.7, 95% CI 33.4 to 162.1; p = 0.004). HIVST uptake was 74.7% (2,956/3,960), with few adverse events (0.6%, 18/2,955) and at US$5.70 per HIVST kit distributed. The main limitations include the use of self-reported HIV testing outcomes and lack of baseline measurement for the primary outcome. CONCLUSIONS: In this study, we found that community-led HIVST was effective, safe, and affordable, with population impact and coverage rapidly realised at low cost. This approach could enable community HIV testing in high HIV prevalence settings and demonstrates potential for economies of scale and scope. TRIAL REGISTRATION: Clinicaltrials.gov NCT03541382